Irinotecan and Flavopiridol in Treating Patients With Advanced Liver Cancer

OBJECTIVES:

Primary

• Determine the time to progression in patients with advanced hepatocellular carcinoma treated with irinotecan and flavopiridol.

Secondary

• Determine the response rate and overall survival in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label, non-randomized study.

Patients receive irinotecan IV over 30 minutes and flavopiridol IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 16-32 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed hepatocellular carcinoma

• Advanced disease
• Measurable disease

• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Prior local therapy (e.g., surgery, hepatic arterial embolization, radiofrequency ablation, or cryoablation) allowed provided therapy was completed ≥ 8 weeks before study entry AND ≥ 1 of the following conditions are met:

• Target lesion was not subjected to local therapy
• 25% increase in the size of target lesion within the field of prior local therapy

• Lesions treated with external beam radiotherapy are not acceptable as target lesions
• Child-Pugh class A or B status if liver cirrhosis is present

• Score 7 or 8 only
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 75,000/mm^3
• WBC ≥ 3,000/mm^3

Hepatic

• See Disease Characteristics
• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin ≤ 1.5 mg/dL

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No deep vein thrombosis within the past 6 months

• Patients maintained on anticoagulation therapy for an event that occurred more than 6 months ago are eligible
• No myocardial infarction within the past 6 months
• No cardiac arrhythmia within the past 6 months

• Rate-controlled atrial fibrillation allowed if stable for at least 6 months

Pulmonary

• No pulmonary embolus within the past 6 months

• Patients maintained on anticoagulation therapy for an event that occurred more than 6 months ago are eligible

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to flavopiridol or irinotecan
• No clinically significant gastrointestinal bleeding requiring hospitalization within the past month
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No other malignancy within the past 3 years except carcinoma in situ of the cervix, adequately treated basal cell skin cancer, or superficial bladder tumors [Ta, Tis, or T1]

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior systemic biologic therapy

Chemotherapy

• No prior systemic chemotherapy for hepatocellular carcinoma
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics
• No prior organ allograft

Other

• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent vitamins, antioxidants, or herbal preparations and supplements

• Single-tablet multivitamin allowed
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies